CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.
CD56/NCAM mediates cell migration of human NK cells by promoting integrin-mediated adhesion turnover.
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CD56/NCAM 通过促进整合素介导的粘附周转来介导人类 NK 细胞的细胞迁移。
DOI：
10.1101/2023.11.21.567714
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mace,EmilyM
中科院分区：
文献类型：
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作者：
Martinez,AmeraL;Shannon,MichaelJ;Sloan,Tyler;Mace,EmilyM
自然杀伤（NK）细胞巡逻组织，介导病毒感染和致瘤细胞的溶解。人NK细胞通常通过其神经细胞粘附分子（NCAM，CD 56）的表达来鉴定，然而，尽管其在NK细胞上普遍表达，但CD 56仍然是免疫细胞上知之甚少的蛋白质。CD 56先前已被证明在NK细胞的细胞毒性功能和细胞迁移中发挥作用。具体而言，CD 56缺陷型NK细胞在基质细胞上的细胞迁移受损，并且CD 56定位于在基质上迁移的NK细胞的尾足。在这里，我们表明，CD 56是所需的NK细胞迁移ICAM-1，并建立持久的细胞极性和单向肌动蛋白流。CD 56的细胞内结构域（NCAM-140）是其功能所需的，并且CD 56的损失导致肌动蛋白灶扩大和磷酸化Pyk 2的隔离，伴随着活化的LFA-1簇的大小和频率增加。总之，这些数据确定了CD 56通过调节肌动蛋白动力学和整联蛋白周转在调节人NK细胞迁移中的作用。
Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet, despite its ubiquitous expression on NK cells, CD56 remains a poorly understood protein on immune cells. CD56 has been previously demonstrated to play roles in NK cell cytotoxic function and cell migration. Specifically, CD56-deficient NK cells have impaired cell migration on stromal cells and CD56 is localized to the uropod of NK cells migrating on stroma. Here, we show that CD56 is required for NK cell migration on ICAM-1 and is required for the establishment of persistent cell polarity and unidirectional actin flow. The intracellular domain of CD56 (NCAM-140) is required for its function, and the loss of CD56 leads to enlarged actin foci and sequestration of phosphorylated Pyk2, accompanied by increased size and frequency of activated LFA-1 clusters. Together, these data identify a role for CD56 in regulating human NK cell migration through modulation of actin dynamics and integrin turnover.